Adenoid Cystic Carcinoma, Erbitux, and Particle Therapy

Adenoid Cystic Carcinoma Clinical Trial

— ACCEPT  

Official title:

Combined Treatment of Adenoid Cystic Carcinoma With Cetuximab and IMRT Plus C12 Heavy Ion Boost - ACCEPT - (ACC, Erbitux, and Particle Therapy); Phase I/II Feasibility Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01192087
• Other study ID #: ACCEPT
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: August 30, 2010
• Last updated: April 23, 2013
• Start date: June 2012
• Est. completion date: July 2017

Study information

• Verified date: April 2013
• Source: Heidelberg University
• Contact: Alexandra D Jensen, MD MSc
• Phone: +49-6221-56-
• Email: alexandra.jensen[@]med.uni-heidelberg.de
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-InstitutGermany: Federal Office for Radiation Protection
• Study type: Interventional

Clinical Trial Summary

The ACCEPT (A(denoid) c(ystic) c(arcinoma), E(rbitux, and) p(article) t(herapy))-trial is a prospective, monocentric phase I/II feasibility trial evaluating toxicity and efficacy in the combined treatment of intensity-modulated radiation therapy (IMRT) and carbon ion (C12) boost with the epidermal growth factor receptor (EGFR) antibody cetuximab. The primary objective of the study is to explore the toxicity of the combined modality regimen consisting of heavy ion therapy / IMRT and EGFR antibody immunotherapy, by assessing the rate of patients with mucositis or any other toxicity of severity grade 3 or 4 according to NCI CTCAE V. 4. Secondary endpoints include local control, distant control, overall disease-free survival, overall survival

Description:

Treatment with novel radiotherapeutic technologies could increase local control in adenoid cystic carcinoma of the head and neck. Especially combined treatment with intensity-modulated radiation therapy and heavy ion (C12) boost to the primary tumor or previous tumor bed could be established as the treatment of choice in this disease.

Unfortunately, therapeutic results in the treatment of adenoid cystic carcinoma are still hampered by the occurrence of distant metastases (predominantly in the lungs) which, though progressing comparatively slowly, still limit the patient's life expectancy. Most adenoid cystic carcinomas (> 80%) though, exhibit over-expression of EGFR receptors and hence provide an approach for systemic treatment. In this prospective phase II trial, the application of the EGFR antibody cetuximab will be evaluated in combination with the established treatment of intensity-modulated radiation therapy plus C12 heavy ion boost.

The trial aims at evaluation of toxicity and feasibility of the combined treatment, as primary endpoint, as well as local control and disease-free survival as secondary endpoints.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 49
• Est. completion date: July 2017
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion criteria

• Histologically proven, or surgically resected adenoid-cystic carcinoma of the head and neck and

• macroscopic or microscopic residual tumor (R1/ R2) or

• Tumor stage >T3/T4 or

• perineural invasion and

• M0 stage

• Written informed consent

• Age between 18 and 70 years

• Karnofsky Index = 70%

• Adequate bone-marrow, liver, and kidney function:

• neutrophils = 1.5 x 109/L,

• thrombocytes = 100 x 109/L,

• haemoglobin = 10.0 g/dL

• bilirubin = 2.0 g/dL

• SGOT, SGPT, AP, gamma-GT = 3 x ULN

• serum creatinine = 1.5 mg/dL

• effective contraception

Exclusion Criteria:

• Prior RT or chemotherapy for tumors of the head and neck

• R0 resection

• M1 (distant metastases)

• prior immunotherapy

• signs of active infection

• other serious illnesses

• Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction within the last twelve months, significant arrhythmias)

• Significant neurologic or psychiatric disorders including dementia or seizures

• Active disseminated intravascular coagulopathies

• Other serious underlying medical conditions prohibiting the patient's participation in the trial according to the judgement of the investigators

• Active participation in another clinical trial within the past 30 days

• Known allergic/ hypersensitivity reactions to non-human proteins

• Women: pregnant (Positive serum/ urine beta-HCG ) or breast-feeding,

• Known drug abuse,

• Other previous malignancy within the past 5 years, with exception of a history of a previous, adequately treated, basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix,

• Legal incapacity or limited legal capacity,

• Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenoid Cystic Carcinoma
• Carcinoma
• Carcinoma, Adenoid Cystic

Intervention

Drug:
• Cetuximab
cetuximab initial dose (7 days prior to RT treatment start): 400 mg/m² body surface cetuximab weekly doses (from RT treatment start throughout radiation treatment): 250 mg/m² body surface

Locations

Country	Name	City	State
Germany	Dept. of Radiation Oncology	Heidelberg

Sponsors (4)

Lead Sponsor	Collaborator
Heidelberg University	Dept. of Radiation Oncology, INF 400, 69120 Heidelberg, Germany, Merck KGaA, University Hospital Heidelberg

Country where clinical trial is conducted

Germany, 

References & Publications (26)

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Alcedo JC, Fábrega JM, Arosemena JR, Urrutia A. Imatinib mesylate as treatment for adenoid cystic carcinoma of the salivary glands: report of two successfully treated cases. Head Neck. 2004 Sep;26(9):829-31. — View Citation

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Chen AM, Bucci MK, Weinberg V, Garcia J, Quivey JM, Schechter NR, Phillips TL, Fu KK, Eisele DW. Adenoid cystic carcinoma of the head and neck treated by surgery with or without postoperative radiation therapy: prognostic features of recurrence. Int J Radiat Oncol Biol Phys. 2006 Sep 1;66(1):152-9. — View Citation

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Haddad RI, Posner MR, Busse PM, Norris CM Jr, Goguen LA, Wirth LJ, Blinder R, Krane JF, Tishler RB. Chemoradiotherapy for adenoid cystic carcinoma: preliminary results of an organ sparing approach. Am J Clin Oncol. 2006 Apr;29(2):153-7. — View Citation

Hotte SJ, Winquist EW, Lamont E, MacKenzie M, Vokes E, Chen EX, Brown S, Pond GR, Murgo A, Siu LL. Imatinib mesylate in patients with adenoid cystic cancers of the salivary glands expressing c-kit: a Princess Margaret Hospital phase II consortium study. J Clin Oncol. 2005 Jan 20;23(3):585-90. — View Citation

Huber PE, Debus J, Latz D, Zierhut D, Bischof M, Wannenmacher M, Engenhart-Cabillic R. Radiotherapy for advanced adenoid cystic carcinoma: neutrons, photons or mixed beam? Radiother Oncol. 2001 May;59(2):161-7. — View Citation

Jäkel O, Krämer M, Schulz-Ertner D, Heeg P, Karger CP, Didinger B, Nikoghosyan A, Debus J. Treatment planning for carbon ion radiotherapy in Germany: review of clinical trials and treatment planning studies. Radiother Oncol. 2004 Dec;73 Suppl 2:S86-91. — View Citation

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Münter MW, Schulz-Ertner D, Hof H, Nikoghosyan A, Jensen A, Nill S, Huber P, Debus J. Inverse planned stereotactic intensity modulated radiotherapy (IMRT) in the treatment of incompletely and completely resected adenoid cystic carcinomas of the head and neck: initial clinical results and toxicity of treatment. Radiat Oncol. 2006 Jun 6;1:17. — View Citation

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Schulz-Ertner D, Nikoghosyan A, Jäkel O, Haberer T, Kraft G, Scholz M, Wannenmacher M, Debus J. Feasibility and toxicity of combined photon and carbon ion radiotherapy for locally advanced adenoid cystic carcinomas. Int J Radiat Oncol Biol Phys. 2003 Jun 1;56(2):391-8. — View Citation

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Younes MN, Park YW, Yazici YD, Gu M, Santillan AA, Nong X, Kim S, Jasser SA, El-Naggar AK, Myers JN. Concomitant inhibition of epidermal growth factor and vascular endothelial growth factor receptor tyrosine kinases reduces growth and metastasis of human salivary adenoid cystic carcinoma in an orthotopic nude mouse model. Mol Cancer Ther. 2006 Nov;5(11):2696-705. — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with acute adverse effects as a Measure of toxicity	The primary objective is to explore the toxicity of the combined treatment consisting of heavy ion therapy / IMRT and cetuximab by assessing the rate of patients with mucositis or any other toxicity of severity grade 3 or 4 according to NCI CTCAE V. 4.; Acute treatment effects will be evaluated 6 weeks and late effects 3 years post completion of treatment	6 weeks post completion of therapy	Yes
Primary	Number of Participants with late adverse effects as a Measure of toxicity	The primary objective is to explore the toxicity of the combined treatment consisting of heavy ion therapy / IMRT and cetuximab by assessing the rate of patients with mucositis or any other toxicity of severity grade 3 or 4 according to NCI CTCAE V. 4.; Acute treatment effects will be evaluated 6 weeks and late effects 3 years post completion of treatment	3 years post completion of treatment	Yes
Secondary	local relapse-free survival	Local relapse-free survival will be defined as the time from the initial dose of study therapy to the time of locoregional disease progression or relapse or death, or to the date of last assessment without any such event (censored observation)	at 3 years post treatment	No
Secondary	distant relapse-free survival	Distant relapse-free survival will be defined as the time from the initial dose of study therapy to the time of distant metastasis detection or death, or to the date of last assessment without any such event (censored observation)	at 3 years post treatment	No
Secondary	overall disease-free survival	Distant disease-free survival will be defined as the time from the initial dose of study therapy to the time of any detection of adenoid cystic carcinoma relapse or development of secondary cancer or death, or to the date of last assessment without any such event (censored observation)	at 3 years post treatment	No
Secondary	overall survival	The duration of survival will be determined by measuring the time interval from initial dose of study therapy to the date of death of any cause or last observation (censored)	at 3 years post treatment	No